Integrated Gene Sequencing Chip for Automated Droplet Processing
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Solution Overview
Problem
Existing gene sequencing technologies require separate chips for library preparation and sequencing, leading to increased reagent consumption, manual operations, and high costs due to inaccurate metering and manual handling, which hinders automation and cost reduction.
Innovation Solution
A gene sequencing chip integrating manipulation electrode arrays for handling liquid drops, enabling simultaneous library preparation and sequencing on a single chip using digital microfluidic techniques, allowing precise control over liquid drop movements and reactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If separate chips are used for library preparation and sequencing, then the fabrication of each chip is simple, but the reagent consumption increases and manual operations are required
Solution Approach 1:
The patent merges library preparation and sequencing functions into a single integrated chip that contains both a library preparation reaction region and a sequencing reaction region. This allows multiple operations to be performed on one chip, reducing reagent consumption by eliminating manual transfer steps and enabling automated continuous processing without requiring separate chips for each function.
Solution Approach 2:
The integrated chip is designed with multi-functionality, incorporating both library preparation and sequencing capabilities in a single device. The chip can perform multiple operations including library preparation, amplification, and sequencing reactions without requiring manual intervention, thereby reducing reagent loss while maintaining manufacturing feasibility.
2Ease of operation
If manual loading is used to transfer library to sequencing chip, then the operation is simple to perform, but the sequencing period increases and automation is reduced
Solution Approach 1:
By combining library preparation and sequencing on a single integrated chip, the patent eliminates the manual loading step required to transfer libraries between separate chips. The integrated design enables automated continuous processing where reactions proceed sequentially within the same device, significantly increasing sequencing speed while maintaining operational simplicity through automated fluid handling.
Solution Approach 2:
The integrated chip incorporates automated fluid handling systems that perform library transfer and reagent delivery without manual intervention. The system uses electric field-driven liquid drop manipulation to automatically move samples and reagents between reaction regions, enabling self-service operation that increases productivity while maintaining ease of use through programmatic control.
3Ease of operation
If manual transfer is used for library loading, then the operation is straightforward, but reagent cost and time cost increase
Solution Approach 1:
The integrated chip design merges library preparation and sequencing operations, eliminating the time-consuming manual transfer step. The system performs automated library loading and processing within the same device, reducing time cost while maintaining operational simplicity through automated fluid manipulation and programmatic control of reaction sequences.
4Device complexity
If electroosmotic flow or pressure-driven channels are used, then the chip structure is simple, but liquid drop manipulation accuracy decreases and reagent consumption increases
Solution Approach 1:
The patent replaces pressure-driven or electroosmotic flow mechanisms with electric field-driven digital microfluidic manipulation. Individual manipulation electrodes control liquid drops with high precision by applying localized electric fields, enabling accurate metering and positioning of reagents while maintaining relatively simple chip structure through planar electrode arrays integrated into the substrate.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Facilitates efficient, automated gene sequencing with reduced reagent consumption and cost by integrating library preparation and sequencing on a single chip, achieving accurate metering and streamlined processes.
Implementation Method 1
The lower substrate comprises a liquid drop operation region, the liquid drop operation region comprises: at least one first manipulation electrode array, each first manipulation electrode array comprising a plurality of first manipulation electrodes arranged in a row in a first direction and spaced apart from each other, the first manipulation electrode array being configured to move the raw material liquid drops and the gene library preparation reagent liquid drops
Implementation Method 2
a rectangular ring-shaped array comprising a plurality of third manipulation electrodes spaced apart from each other and forming a rectangular shape, the rectangular ring-shaped array being configured to mix the raw material liquid drops and the gene library preparation reagent liquid drops
Data Source
AI summary
A gene sequencing chip is provided, which includes: an upper substrate including a plurality of liquid inlets for inletting liquid drops; a lower substrate opposite to the upper substrate and spaced therefrom by a gap, the gap being provided for allowing the liquid drops to move therein, the lower substrate including a liquid drop operation region, the liquid drop operation region including a manipulation electrode array. The manipulation electrode array includes multiple first manipulation electrode array for preparing a gene library, multiple second manipulation electrode array for sequencing the gene library which is prepared, each first sub-array being adjacent to one of the multiple second manipulation electrode array. Based on the gene sequencing chip provided in this disclosure, operations to tiny liquid drops such as movement, fusion and splitting can be accurately manipulated by using digital microfluidic techniques, and all steps of the gene sequencing from library preparation to gene sequencing can be completed on one chip.